Although it has been known for several decades that the pituitary plays a central role in the regulation of spermatogenesis, and that spermatogenesis is an androgen dependent process, there remains much uncertainty about the relative contributions of testosterone and pituitary hormones, and about their interactions, during the spermatogenic process. For example, while it is established that testosterone is required to maintain ongoing spermatogenesis in established that testosterone is required to maintain ongoing spermatogenesis in the adult rat or to restore spermatogenesis in the regressed testes of adult rats, an unresolved issue is whether FSH and/or other pituitary factors are also required; and, if so, the extent to which they are required. The specific aims of this proposal are to determine the extent to which spermatogenesis can be and quantitatively maintained with testosterone in intact rats in which LH, FSH, growth hormone (GH) and/or prolactin are selectively eliminated; and the extent to which spermatogenesis can be quantitatively restored with testosterone in rats lacking LH, FSH, GH and/or prolactin. We propose experiments that will utilize active immunization to suppress LH or GnRH and thus to selectively suppress pituitary production of LH alone or of LH and FSH. Using these immunized rats, we will determine: 1) whether testosterone is able to quantitatively maintain or restore spermatogenesis after selective elimination of prolactin by the administration of bromocriptine, and/or selective elimination of GH by active immunization against ovine GH; and 2) whether prolactin and GH act synergistically during the maintenance and/or restoration of spermatogenesis. We will also ask whether the restoration of spermatogenesis in these animals results in functionally normal spermatozoa. Taken together, this information will greatly enhance our understanding of the hormonal regulation of spermatogenesis, and in particular of the interactions between androgen and pituitary factors.